Dataset Information

A new user cohort study comparing the safety of long-acting inhaled bronchodilators in COPD.

ABSTRACT:

Objective

To investigate a possible increased risk observed in tiotropium clinical trials of stroke and other adverse events.

Design

New users of long-acting anticholinergic therapy (tiotropium HandiHaler®) were compared with new users of long-acting ?-agonist (LABA) monotherapy, and propensity scores were used to control confounding.

Setting

UK healthcare system general practitioner electronic medical record database.

Participants

10?840 patients newly prescribed tiotropium (n=4767) or LABA (n=6073), at least 40 years old, and not having asthma as their only respiratory illness.

Primary and secondary outcome measures

Incidence rates of total stroke, myocardial infarction, angina and other adverse events.

Results

Tiotropium was associated with increased rates of stroke (HR=1.49, 95% CI 0.91 to 2.45), angina (HR=1.38, 95% CI 0.88 to 2.16) and myocardial infarction (HR=1.26, 95% CI 0.72 to 2.21). Groups had similar rates of chronic obstructive pulmonary disease exacerbation (HR=0.95, 95% CI 0.80 to 1.12) and pneumonia (HR=0.96, 95% CI 0.58 to 1.58). Tiotropium was associated with a lower rate of total mortality (HR=0.70, 95% CI 0.56 to 0.89) and asthma exacerbations (HR=0.46, 95% CI 0.36 to 0.57) than users of LABA.

Conclusion

Small increased risks of serious ischaemic cardiovascular events have been reported with inhaled anticholinergic medication from randomised and nonrandomized studies of ipratropium, tiotropium HandiHaler® and tiotropium Respimat®. Additional research is needed to understand the full extent of cardiovascular effects of inhaled anticholinergic medications and the patients who may be most susceptible.

SUBMITTER: Jara M

PROVIDER: S-EPMC3364448 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

A new user cohort study comparing the safety of long-acting inhaled bronchodilators in COPD.

Jara Michele M Wentworth Charles C Lanes Stephan S

BMJ open 20120522 3

<h4>Objective</h4>To investigate a possible increased risk observed in tiotropium clinical trials of stroke and other adverse events.<h4>Design</h4>New users of long-acting anticholinergic therapy (tiotropium HandiHaler®) were compared with new users of long-acting β-agonist (LABA) monotherapy, and propensity scores were used to control confounding.<h4>Setting</h4>UK healthcare system general practitioner electronic medical record database.<h4>Participants</h4>10 840 patients newly prescribed ti ...[more]

PMID: 22619266

Similar Datasets

Project description:IntroductionObservational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs.ObjectiveTo estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.MethodsPneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding.SettingUnited Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010). New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up.Outcomessevere pneumonia (primary) and any pneumonia (secondary).ResultsFollowing adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.ConclusionsThe results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time. This risk must be weighed against the benefits when prescribing ICS to patients with COPD.

Project description:Importance:The associations between cardiovascular disease (CVD) and inhaled long-acting ?2-agonists (LABAs) or long-acting antimuscarinic antagonists (LAMAs) in chronic obstructive pulmonary disease (COPD) are greatly debated. Pivotal and relevant randomized clinical trials included prior LABA or LAMA users and excluded patients with baseline CVD; therefore, cardiovascular events arising from first-time LABA or LAMA use, if any, could not be observed. There is an urgent need to examine whether new use of and duration since initiating LABAs and LAMAs could act as important determinants of cardiovascular events. Objective:To investigate risk of CVD associated with LABAs and LAMAs, focusing on the initiation and duration of LABA and LAMA therapies. Design, Setting, and Participants:This nested case-control study included 284?220 LABA-LAMA-naïve patients with COPD at least 40 years old (mean age, 71.4 years; 68.9% men), retrieved from the Taiwan National Health Insurance Research Database for health care claims from 2007 to 2011. Exposure:LABA or LAMA use was measured in the year preceding the event or index date, stratified by duration since initiation of LABA or LAMA treatment, new and prevalent users, concomitant COPD medications, and individual agents. Main Outcomes and Measures:Cases with inpatient or emergency care visits for coronary artery disease, heart failure, ischemic stroke, or arrhythmia were identified and individually matched to 4 randomly selected controls. Conditional logistic regressions were performed to estimate odds ratios of CVD from LABA and LAMA treatment. Results:During a mean follow-up of 2.0 years, 37?719 patients with CVD (mean age, 75.6 years; 71.6% men) and 146?139 matched controls (mean age, 75.2 years; 70.1% men) were identified. New LABA and LAMA use in COPD was associated with a 1.50-fold (95% CI, 1.35-1.67; P?<?.001) and a 1.52-fold (95% CI, 1.28-1.80; P?<?.001) increased cardiovascular risk within 30 days of initiation, respectively, whereas the risk was absent, or even reduced with prevalent use. Individual LABA agents, LAMA dosage forms, and concomitant COPD regimens did not differ in the CVD risks. The risk persisted in an alternative case-crossover study and remained across subgroups without CVD history or prior exacerbations. Conclusions and Relevance:New initiation of LABAs or LAMAs in patients with COPD is associated with an approximate 1.5-fold increased severe cardiovascular risk, irrespective of prior CVD status and history of exacerbations.

Dataset Information

A new user cohort study comparing the safety of long-acting inhaled bronchodilators in COPD.

Objective

Design

Setting

Participants

Primary and secondary outcome measures

Results

Conclusion

Publications

A new user cohort study comparing the safety of long-acting inhaled bronchodilators in COPD.

Similar Datasets

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